The purpose of this study is to more clearly define the nature of the immunoregulatory processes that are responsible for the induction of and recovery from Experimental Allergic Encephalomyelitis (EAE). Our studies will focus on the cell responsible for induction of disease and will attempt to determine if this cell acts in concert with lymphocyte subpopulations for the full expression of disease. We will also attempt to evaluate the immune response in animals that inhibits the differentiation of the disease inducing cell. The cell population most appropriate for the study is the effector cell population that can be recovered from antigen stimulated spleen cell cultures. The in vivo activity of these cells is dependent on the culture period. During the culture period cell differentiation apparently develops such that the resulting effector cell population no longer responds to currently postulated immunoregulation. We will also include in our investigation experiments designed to analyze the in vitro events that lead to the development of the effector cells that can only transfer clinical disease following the in vitro culture period. The analysis of the regulatory and cooperative events that are required for the in vitro development of the effector cell and the evaluation of the requirements for effector cell function in vivo will also enable us to measure developing immunoregulation active against the effector cell (or precursors of EAE. These studies will be carried out in the rat model of EAE and will employ normal as well as athymic animals for experimentation.